RESUMEN
This article involved a broad search of applied sciences for milestone technologies we deem to be the most significant innovations applied by the North American pork industry, during the past 10 to 12 years. Several innovations shifted the trajectory of improvement or resolved significant production limitations. Each is being integrated into practice, with the exception being gene editing technology, which is undergoing the federal approval process. Advances in molecular genomics have been applied to gene editing for control of porcine reproductive and respiratory syndrome and to identify piglet genome contributions from each parent. Post-cervical artificial insemination technology is not novel, but this technology is now used extensively to accelerate the rate of genetic progress. A milestone was achieved with the discovery that dietary essential fatty acids, during lactation, were limiting reproduction. Their provision resulted in a dose-related response for pregnancy, pregnancy maintenance and litter size, especially in maturing sows and ultimately resolved seasonal infertility. The benefit of segregated early weaning (12 to 14 days of age) was realized for specific pathogen removal for genetic nucleus and multiplication. Application was premature for commercial practice, as piglet mortality and morbidity increased. Early weaning impairs intestinal barrier and mucosal innate immune development, which coincides with diminished resilience to pathogens and viability later in life. Two important milestones were achieved to improve precision nutrition for growing pigs. The first involved the updated publication of the National Research Council nutrient requirements for pigs, a collaboration between scientists from America and Canada. Precision nutrition advanced further when ingredient description, for metabolically available amino acids and net energy (by source plant), became a private sector nutrition product. The past decade also led to fortuitous discoveries of health-improving components in ingredients (xylanase, soybeans). Finally, two technologies converged to facilitate timely detection of multiple pathogens in a population: oral fluids sampling and polymerase chain reaction (PCR) for pathogen analysis. Most critical diseases in North America are now routinely monitored by oral fluid sampling and prepared for analysis using PCR methods.
Asunto(s)
Crianza de Animales Domésticos/economía , Industria de Alimentos , Carne Roja/economía , Animales , América del Norte , PorcinosAsunto(s)
Pie/diagnóstico por imagen , Cuerpos Extraños/diagnóstico por imagen , Tétanos/diagnóstico , Niño , Desbridamiento , Traumatismos de los Pies/cirugía , Cuerpos Extraños/cirugía , Humanos , Inmunoglobulinas/uso terapéutico , Masculino , Tétanos/terapia , Toxoide Tetánico/uso terapéutico , UltrasonografíaRESUMEN
Pycnodysostosis is a rare autosomal recessive disease due to a mutation in the gene for the enzyme Cathepsin K. It is characterized by short stature, craniofacial dysmorphias, osteosclerosis, and brittle bones. There are only a few reports in the literature describing surgical interventions for long bone fractures in pycnodysostosis patients, most of which describe intramedullary nail treatment of isolated long bone fractures. We describe a case in which a pregnant female with pycnodysostosis presented with a shaft fracture of the left femur following minor trauma and a history of increasing thigh pain. Radiographs obtained in the emergency room also revealed an impending subtrochanteric fracture of the contralateral side. The acute left femoral shaft fracture was treated with an adolescent-sized intramedullary nail; it was decided to defer surgery on the contralateral side until after pregnancy. Three months later, the patient had the contralateral femur prophylactically fixated with a plate and screws. One year after the index surgery, both methods demonstrated satisfactory healing both clinically and radiographically. Although we recommend use of an intramedullary nail for long bone fractures in patients with pycnodysostosis, a plate can be utilized if health conditions or skeletal morphology precludes use of a nail.
Asunto(s)
Fracturas del Fémur/etiología , Fracturas Espontáneas/etiología , Complicaciones del Embarazo , Picnodisostosis/complicaciones , Adulto , Placas Óseas , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Fijación Interna de Fracturas/métodos , Fijación Intramedular de Fracturas/métodos , Fracturas Espontáneas/diagnóstico por imagen , Fracturas Espontáneas/cirugía , Fracturas de Cadera/prevención & control , Humanos , Embarazo , RadiografíaRESUMEN
The Beef Improvement Federation recommends residual feed intake (RFI) be calculated from 70-d tests preceded by a 21-d adjustment period. Individual animal feed intake and gain measurements are expensive and time consuming, which limits the number of animals available for national genetic evaluation of feed intake. If a shorter test period of comparable accuracy could be used, the cost would decrease and more animals could be tested annually. The objective of this study was to determine if data from shortened tests is equally as predictive of average daily DMI (ADMI) and RFI values from 70-d tests. Feed intake and weight measures were collected after weaning from Bos taurus bulls, steers, and heifers (n = 612) during four 70-d performance tests. For each individual, ADMI and RFI were calculated. Residual feed intake was calculated by regressing ADMI on metabolic midweight (MMWT) and ADG with the effect of breed included where appropriate. Based on four 70-d intake tests, ADMI, RFI, ADG, and MMWT were evaluated using shortened test lengths in a post hoc analysis where shortened test lengths were imposed on the full-period tests. The ADMI, RFI, ADG, and MMWT values from the full 70-d test were regressed on ADMI, RFI, ADG, and MMWT values resulting from the constructed shorter data subsets. The 8 subsets ranged from 14 to 56 d in length. The fixed effects of test, breed, animal's origin, and sex were included in each comparison for ADMI, ADG, and MMWT. Estimates for regression coefficients of ADMI values from a full test on various subsets ranged from 0.63 to 1.02. Likewise, estimated coefficients obtained from the regression of full test RFI, ADG, and MMWT values on subsets ranged from 0.50 to 1.00, 0.09 to 0.85, and 0.48 to 1.02, respectively. We conclude that ADMI values from a 42-d test ( < 0.0001) and RFI values from a 56-d test (P < 0.0001) adequately predict ADMI and RFI when compared to a 70-d test. These results suggest that testing periods of 42 d for determining ADMI and 56 d for RFI could ultimately reduce testing costs and result in collection of data on a larger number of animals per year, in turn resulting in more data for genetic evaluation.
Asunto(s)
Peso Corporal/fisiología , Bovinos/fisiología , Ingestión de Alimentos/fisiología , Conducta Alimentaria/fisiología , Aumento de Peso/fisiología , Factores de Edad , Alimentación Animal , Animales , Peso Corporal/genética , Bovinos/genética , Ingestión de Alimentos/genética , Femenino , Masculino , Análisis de Regresión , Factores de Tiempo , Destete , Aumento de Peso/genéticaRESUMEN
Estimates of genetic parameters for number of stillborns (NSB) in relation to litter size (LS) were obtained with random regression models (RRM). Data were collected from 4 purebred Duroc nucleus farms between 2004 and 2008. Two data sets with 6,575 litters for the first parity (P1) and 6,259 litters for the second to fifth parity (P2-5) with a total of 8,217 and 5,066 animals in the pedigree were analyzed separately. Number of stillborns was studied as a trait on sow level. Fixed effects were contemporary groups (farm-year-season) and fixed cubic regression coefficients on LS with Legendre polynomials. Models for P2-5 included the fixed effect of parity. Random effects were additive genetic effects for both data sets with permanent environmental effects included for P2-5. Random effects modeled with Legendre polynomials (RRM-L), linear splines (RRM-S), and degree 0 B-splines (RRM-BS) with regressions on LS were used. For P1, the order of polynomial, the number of knots, and the number of intervals used for respective models were quadratic, 3, and 3, respectively. For P2-5, the same parameters were linear, 2, and 2, respectively. Heterogeneous residual variances were considered in the models. For P1, estimates of heritability were 12 to 15%, 5 to 6%, and 6 to 7% in LS 5, 9, and 13, respectively. For P2-5, estimates were 15 to 17%, 4 to 5%, and 4 to 6% in LS 6, 9, and 12, respectively. For P1, average estimates of genetic correlations between LS 5 to 9, 5 to 13, and 9 to 13 were 0.53, -0.29, and 0.65, respectively. For P2-5, same estimates averaged for RRM-L and RRM-S were 0.75, -0.21, and 0.50, respectively. For RRM-BS with 2 intervals, the correlation was 0.66 between LS 5 to 7 and 8 to 13. Parameters obtained by 3 RRM revealed the nonlinear relationship between additive genetic effect of NSB and the environmental deviation of LS. The negative correlations between the 2 extreme LS might possibly indicate different genetic bases on incidence of stillbirth.
Asunto(s)
Tamaño de la Camada/genética , Modelos Genéticos , Mortinato/veterinaria , Porcinos/genética , Porcinos/fisiología , Animales , Femenino , Paridad , Linaje , Embarazo , Análisis de Regresión , Mortinato/genéticaRESUMEN
Genetic parameters for daily feed intake (DFI, g/day) and daily gain (DG, g/day) were estimated using records of 1916 Duroc boars from electronic feeder stations. Management was limited and resulted in varied ranges of age and weight on test. Boars were housed in 102 pens, each equipped with one feeder, and allowed ad libitum feeding. Weekly averages of DFI and DG were used due to large variation in daily records. Six traits were defined as DFI and DG during 85-106 (period 1), 107-128 (period 2) and 129-150 days of age (period 3). A six-trait model included age as a linear and a quadratic covariate for DFI and a linear covariate for DG with a fixed effect of year-week-pen and random effects of litter, additive genetic animal and permanent environmental animal. Variance components were estimated by a Bayesian approach using Gibbs sampling algorithm. Estimates of heritability for respective periods were 18%, 12% and 10% for DFI and 21%, 11% and 10% for DG. Genetic correlations between DFI and DG in the same period were 0.70, 0.73 and 0.32 for the respective periods. DFI and DG obtained from automatic feeders can be analysed to reveal variation across testing periods by using weekly averages when many monthly averages are incomplete.
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Alimentación Animal/estadística & datos numéricos , Cruzamiento/métodos , Ingestión de Alimentos/fisiología , Sus scrofa/genética , Aumento de Peso/fisiología , Factores de Edad , Análisis de Varianza , Crianza de Animales Domésticos/instrumentación , Animales , Teorema de Bayes , Cruzamiento/estadística & datos numéricos , Modelos Genéticos , Análisis de Regresión , Sus scrofa/fisiologíaRESUMEN
This study examined the utility of serial weights from FIRE (Feed Intake Recording Equipment, Osborne Industries, Inc., Osborne, KS, USA) stations for an analysis of daily gain. Data included 884 132 body weight records from 3888 purebred Duroc pigs. Pigs entered the feeder station at age 77-149 days and left at age 95-184 days. A substantial number of records were abnormal, showing body weight close to 0 or up to twice the average weight. Plots of body weights for some animals indicated two parallel growth curves. Initial editing used a robust regression, which was a two-step procedure. In the first step, a quadratic growth curve was estimated assuming small or 0 weights for points far away from the curve; the process is iterative. In the second step, weights more than 1.5 SD from the estimated growth curve were treated as outliers. The retained body weight records (607,597) were averaged to create average daily weight (170,443) and then used to calculate daily gains (152,636). Additional editing steps included retaining only animals with >or=50 body weight records and SD of the daily gain Asunto(s)
Crianza de Animales Domésticos/métodos
, Peso Corporal/genética
, Porcinos/crecimiento & desarrollo
, Porcinos/genética
, Crianza de Animales Domésticos/instrumentación
, Animales
, Análisis de Regresión
, Factores de Tiempo
, Aumento de Peso/genética
RESUMEN
Social genetic relationships among average daily gain (ADG, g) and feeding pattern as daily feed intake (DFI, g), daily feeder occupation time (DOT, min), and daily feeding rate (DFR, g/min) were examined using records of 547 Duroc boars. Single-trait animal models were fitted differently for traits, including or excluding social genetic effects, random or fixed pen effects, with covariates of pen sizes and initial age or weight. Genetic parameters for feeding pattern were estimated by restricted maximum likelihood. Six sets of parameters for ADG based on literature estimates were used due to difficulty in untangling confounded effects. Positive and negative signs of direct-social genetic covariances were interpreted as heritable cooperation and competition, respectively. Dominant and subordinate pigs were classified as pigs with higher direct and social genetic values, respectively. Correlations of estimated breeding values between ADG and DFI, DOT, and DFR were 0.46, 0.04 and 0.29 for dominant pigs. Given heritable cooperation, subordinate pigs tended to increase feed intake (r = 0.36) and eating rate (r = 0.25). Given heritable competition, subordinate pigs fail to compensate for the competition with decreased feed intake (r = -0.53). The slow eating rate (r = -0.31) was considered as a consequence of eating during less busy hour of feeding.
Asunto(s)
Peso Corporal/genética , Conducta Alimentaria/fisiología , Jerarquia Social , Animales , MasculinoRESUMEN
The objective of this study was to describe genetic variability of pig carcass weight as a function of heat stress. Data included carcass weights of 23,556 crossbred pigs [Duroc x (Landrace x Large White)] raised on 2 farms in North Carolina and harvested from May 2005 through December 2006. Weather data were obtained from a weather station located about 20 km from the furthest farm. Weekly heat load was calculated as degrees of average temperature-humidity index (THI) in excess of 18 degrees C. The total heat load (H) was the sum of heat loads for 10 wk before harvest. Variance components were estimated with 3 models: univariate (UNI)-not accounting for heat stress, 2-trait (MT2), and random regression (RR). In all of the models, effects included contemporary group, sex, age at harvest, sire, and litter. In MT2, observations in months in which heat stress was observed ("hot") and not observed ("cold") were treated as separate traits. Heat stress was observed in the months of August to November 2005, as well as July to October 2006. No heat stress was observed in the months of May to July 2005, January to June 2006, and November to December 2006. The RR model added a random regression on heat load for the sire effect. Heat load was adjusted to a scale ranging from 0 (no heat stress) to 5 (greatest heat stress). The heritability estimate +/- SE of carcass weight in UNI was 0.17 +/- 0.01. In MT2, the estimates were 0.14 +/- 0.01 for "cold" and 0.28 +/- 0.01 for "hot"; the genetic correlation between carcass weight in "hot" and "cold" months was 0.42 +/- 0.13. The heritability estimates obtained with RR were 0.20 +/- 0.11, 0.19 +/- 0.15, and 0.51 +/- 0.17 for H = 0, 2.5, and 5, respectively. The genetic correlation between the performance in "cold" months (H = 0), and performance under maximum heat load (H = 5) was 0.02, between H = 0 and intermediate heat load (H = 2.5) was 0.52, and between H = 2.5 and H = 5 was 0.86. Rank correlations between EPD derived from the different models ranged from 0.82 to 0.94 between carcass weights under similar H, 0.18 to 0.54 between carcass weights under high and low H, and 0.66 to 0.91 between carcass weights of intermediate and high/low H. Heritability for growth was greater under heat stress. Selection for crossbred performance would be optimal when data for periods both in the absence and presence of heat stress were considered.
Asunto(s)
Trastornos de Estrés por Calor/veterinaria , Carne , Porcinos/genética , Animales , Femenino , Variación Genética , Trastornos de Estrés por Calor/genética , Masculino , Carácter Cuantitativo Heredable , Análisis de Regresión , Porcinos/crecimiento & desarrolloRESUMEN
The objective of this study was to quantify the effect of heat stress during the life of a pig on its final weight, as a first step toward a genetic evaluation for heat tolerance. Data included carcass weights of 23,556 crossbred pigs [Duroc x (Landrace x Large White)] raised on 2 farms in North Carolina and slaughtered from May 2005 through December 2006. Weather data were available from a nearby weather station. Lifetime of a pig was assumed to be partitioned into 2 periods. During an initial period, the effect of heat stress was assumed to be negligible or compensated for later. During the second period ending in slaughtering, the ADG was assumed to be affected linearly by heat load. Weekly heat load was calculated as degrees of average temperature-humidity index in excess of a threshold (18 degrees C). The total heat load (H) was the sum of weekly heat loads during the second period. During the months of January to May H was 0; H reached a peak in September. The final BW during the peak of heat stress decreased about 6 kg compared with BW during months of non-heat stress. Weekly and monthly averages of carcass weight generally moved similarly to H. However, there were large fluctuations unrelated to H; the fluctuations were different on the 2 farms. The model included the effects of farm-year of slaughter, sex, age at slaughter, and H, where age at slaughter and H were linear regressions. In analyses, the threshold was varied from 16 to 20 degrees C, and the second period was varied from 8 to 16 wk. The greatest R(2) (10.4%) was at the threshold of temperature-humidity index = 18 degrees C for a period of 10 wk. Varying the threshold and the length of time reduced R(2) less than 1%. Least squares means of year-month and year-week of carcass weight were calculated using a model with the fixed effects farm-year-month or farm-year-week of slaughter, sex, and age at slaughter (linear covariate), and the random effect of birth litter. Changes in BW of finisher pigs due to heat stress can be quantified by H during the last 10 wk of the life of the pig.
Asunto(s)
Peso Corporal/genética , Trastornos de Estrés por Calor/veterinaria , Porcinos/genética , Animales , Femenino , Trastornos de Estrés por Calor/genética , Análisis de los Mínimos Cuadrados , Masculino , Carne , Estaciones del Año , Porcinos/crecimiento & desarrollo , Tiempo (Meteorología)RESUMEN
To study the genetic relationship between three grouped reasons for sow removal (SR) in consecutive parities, accounting for censoring, 13,838 records from Large White sows were analyzed. Data were from seven pure-line farms having, on average, 5.9% unknown SR. Three traits were subjectively defined, each corresponding to a classification of SR (reproductive [RR], nonreproductive [RN], and others [RO]). Records for each trait could take one of five categories, according to parity at removal (0 to 4 or later). A multivariate linear censored model was implemented. The model to estimate (co)variance components and parameters included the effects of year-season, region, contemporary group, and additive genetic effects. The most common SR was related to reproduction (48.5%). Diseases of different origin and cause, old age/parity, and sow death or loss accounted for about 18, 7, and 4% of total culls, respectively. Estimates of variance components showed heterogeneity of additive genetic and residual variances for the three traits. Estimates of heritability were 0.18, 0.13, and 0.15 for RR, RN, and RO, respectively. Genetic correlations between removal codes were high (> or =0.90). Results suggest sizeable additive genetic variances exist for parity at removal and different codes of removal. Different SR reasons seem to operate similarly or as a closely related genetic trait associated with fitness. In particular, RN and RO seem to be genetically indistinguishable. Data structure, definition, and volume are major limitations in studies of sow survival. A multiple-trait censored model is preferred to evaluate reasons of sow disposal. Grouped removal causes seem to be strongly genetically correlated but with heterogeneous variances, suggesting that combining all removal causes and treating the trait as parity at disposal is an alternative approach.
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Crianza de Animales Domésticos/métodos , Crianza de Animales Domésticos/estadística & datos numéricos , Variación Genética/fisiología , Porcinos/genética , Animales , Cruzamiento/métodos , Femenino , Control de Formularios y Registros/métodos , Control de Formularios y Registros/estadística & datos numéricos , Modelos Lineales , Paridad/fisiología , Embarazo , Registros/veterinaria , Reproducción/fisiología , Porcinos/fisiología , Enfermedades de los Porcinos/mortalidadRESUMEN
Records of on-test ADG of Large White gilts were analyzed to estimate variance components of direct and associative genetic effects. Models included the effects of contemporary group (farm-barn-batch), birth litter, pen group, and direct and associative additive genetic effects. The area of each pen was 14 m2. The additive genetic variance was a function of the number of competitors in a group, the additive relationships between the animal performing the record and its pen mates, and the additive relationships between pen mates. To partially account for differences in the number of pen mates, a covariable (qi = 1, 1/n, or 1/n(1/2)) was added to the associative genetic effect. There were 4,946 records from 2,409 litters and 362 pen groups. Pen group size ranged from 12 to 16 gilts. Analyses by REML converged very slowly. A grid search showed that the likelihood function was almost flat when the additive genetic associative effect was fitted. Estimates of direct and associative heritability were 0.15 and 0.03, respectively. Within the BLUPF90 family of programs, the mixed-model equations can be set up directly. For variance component estimation, simple programs (REMLF90 and GIBBSF90) worked without modifications, but more optimized programs did not. Estimates obtained using the three values of qi were similar. With the data structure available for this study and under an environment with relative low competition among animals, accurate estimation of associative genetic effects was not possible. Estimation of competitive effects with large pen size is difficult. The magnitude of competition effects may be larger in commercial populations, where housing is denser and food is limited.
Asunto(s)
Conducta Competitiva/fisiología , Modelos Genéticos , Porcinos/crecimiento & desarrollo , Porcinos/genética , Análisis de Varianza , Animales , Demografía , Femenino , Programas InformáticosRESUMEN
Up to 109,447 records of 49,656 Large White sows were used to evaluate the genetic relationship between number of pigs born dead (BD) and number born alive (BA) in first and later parities. Performance data (n = 30,832) for ultrasound backfat (BF) at the end of the test and days to reach 113.5 kg (AD) were used to estimate their relationships with BD and BA at first parity in a four-trait threshold-linear analysis (TL). Effects were year-farm, contemporary group (CG: farm-farrowing year-farrowing month) and animal additive genetic. At first parity, estimates of heritability were 0.09, 0.09, 0.37, and 0.31 for BA, BD, AD, and BF, respectively. The estimate of genetic correlation between BD and litter size was -0.04 (BD-BA). Corresponding values with test traits were both -0.14 (BD-AD, BD-BF). Estimates of genetic correlation between BA and performance traits were 0.08 (BA-AD) and 0.05 (BA-BF). The two test traits were moderately negatively correlated (-0.22). For later parities, a six-trait (BD, BA in three parities) TL model was implemented. The estimates of additive genetic variances and heritability increased with parity for BD and BA. Estimates of heritabilities were: 0.09, 0.10, and 0.11 for BD, and 0.09, 0.12, and 0.12 for BA in parities one to three, respectively. Estimates of genetic correlations between different parities were high (0.91 to 0.96) for BD, and slightly lower (0.74 to 0.95) for BA. Genetic correlations between BD and BA were low and positive (0.02 to 0.17) for BA in Parities 1 and 2, but negative (-0.04 to -0.10) for BA in Parity 3. Selection for increased litter size should have little effect on farrowing piglet mortality. Intense selection for faster growth and increased leanness should increase farrowing piglet mortality of first-parity sows. A repeatability model with a simple correction for the heterogeneity of variances over parities could be implemented to select against farrowing mortality. The genetic components of perinatal piglet mortality are independent of the ones for litter size in the first parity, and they show an undesirable, but not strong, genetic association in second parity.
Asunto(s)
Variación Genética/fisiología , Tamaño de la Camada/genética , Paridad/fisiología , Mortinato/veterinaria , Porcinos/genética , Animales , Femenino , Masculino , Modelos Genéticos , Análisis Multivariante , Paridad/genética , Embarazo , Carácter Cuantitativo Heredable , Mortinato/genética , Porcinos/fisiologíaRESUMEN
Meat quality traits and palatability characteristics were evaluated on 240 barrows and gilts subjected to one of eight dietary regimens: (1) control (no supplement), (2) vitamin D(3)(D(3)), (3) vitamin E (E), (4) magnesium (Mg), (5) vitamins D(3) and E (D(3)/E), (6) vitamin D(3) and magnesium (D(3)/Mg), (7) vitamin E and magnesium (E/Mg), and (8) vitamins D(3) and E, and magnesium (D(3)/E/Mg). Barrows supplemented with D(3)/E/Mg had the highest (P>0.05) ultimate pH. Those supplemented with E had a higher ultimate pH than those supplemented with D(3)/Mg or the control. Gilts supplemented with Mg had the highest ultimate pH of all of the gilts while those supplemented with D(3) had the lowest. Barrows supplemented with Mg or E had more marbling than those supplemented with D(3) or D/E. Gilts supplemented with Mg had the most marbling when compared to other gilts. At 48 h postmortem, no differences due to dietary treatment were observed in L (∗), a (∗) or b (∗) value, drip loss or purge loss. At 14 days postmortem, no differences due to diet existed in sensory characteristics. Results suggest that supplementation of swine diets with some dietary supplement combinations of containing Mg may have some potential benefit for increasing ultimate pH.
Asunto(s)
Codón sin Sentido , Análisis Mutacional de ADN/métodos , Proteínas Fúngicas/genética , Terminación de la Cadena Péptídica Traduccional , ARN Mensajero , Proteínas de Unión al ARN , Proteínas de Saccharomyces cerevisiae , Técnicas de Cultivo de Célula , Humanos , Modelos Genéticos , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
The SUF13 and SUF14 genes were identified among extragenic suppressors of +1 frameshift mutations. SUF13 is synonymous with MBF1, a single-copy nonessential gene coding for a POLII transcription factor. The suf13-1 mutation is a two-nucleotide deletion in the SUF13/MBF1 coding region. A suf13::TRP1 null mutant suppresses +1 frameshift mutations, indicating that suppression is caused by loss of SUF13 function. The suf13-1 suppressor alters sensitivity to aminoglycoside antibiotics and reduces the accumulation of his4-713 mRNA, suggesting that suppression is mediated at the translational level. The SUF14 gene is synonymous with RPS3, a single-copy essential gene that codes for the ribosomal protein S3. The suf14-1 mutation is a missense substitution in the coding region. Increased expression of S3 limits the accumulation of SUF14 mRNA, suggesting that expression is autoregulated. A frameshift mutation in SUF14 that prevents full-length translation eliminated regulation, indicating that S3 is required for regulation. Using CUP1-SUF14 and SUF14-lacZ fusions, run-on transcription assays, and estimates of mRNA half-life, our results show that transcription plays a minor role if any in regulation and that the 5'-UTR is necessary but not sufficient for regulation. A change in mRNA decay rate may be the primary mechanism for regulation.
Asunto(s)
Mutación del Sistema de Lectura , Genes Fúngicos , Proteínas Ribosómicas/biosíntesis , Proteínas Ribosómicas/genética , Proteínas de Saccharomyces cerevisiae , Supresión Genética , Transactivadores/genética , Regiones no Traducidas 5' , Alelos , Cobre/farmacología , Bases de Datos Factuales , Relación Dosis-Respuesta a Droga , Dosificación de Gen , Modelos Genéticos , Mutación , Fenotipo , Plásmidos/genética , Plásmidos/metabolismo , Regiones Promotoras Genéticas , ARN Mensajero/metabolismo , Factores de Tiempo , Factores de Transcripción , Transcripción Genética , Transformación GenéticaRESUMEN
mRNAs are monitored for errors in gene expression by RNA surveillance, in which mRNAs that cannot be fully translated are degraded by the nonsense-mediated mRNA decay pathway (NMD). RNA surveillance ensures that potentially deleterious truncated proteins are seldom made. NMD pathways that promote surveillance have been found in a wide range of eukaryotes. In Saccharomyces cerevisiae, the proteins encoded by the UPF1, UPF2, and UPF3 genes catalyze steps in NMD and are required for RNA surveillance. In this report, we show that the Upf proteins are also required to control the total accumulation of a large number of mRNAs in addition to their role in RNA surveillance. High-density oligonucleotide arrays were used to monitor global changes in the yeast transcriptome caused by loss of UPF gene function. Null mutations in the UPF genes caused altered accumulation of hundreds of mRNAs. The majority were increased in abundance, but some were decreased. The same mRNAs were affected regardless of which of the three UPF gene was inactivated. The proteins encoded by UPF-dependent mRNAs were broadly distributed by function but were underrepresented in two MIPS (Munich Information Center for Protein Sequences) categories: protein synthesis and protein destination. In a UPF(+) strain, the average level of expression of UPF-dependent mRNAs was threefold lower than the average level of expression of all mRNAs in the transcriptome, suggesting that highly abundant mRNAs were underrepresented. We suggest a model for how the abundance of hundreds of mRNAs might be controlled by the Upf proteins.
Asunto(s)
Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , ARN Helicasas/metabolismo , ARN Mensajero/biosíntesis , Proteínas de Unión al ARN , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Transactivadores/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Perfilación de la Expresión Génica , Análisis de Secuencia por Matrices de Oligonucleótidos , Procesamiento Postranscripcional del ARN , Estabilidad del ARN , ARN Mensajero/clasificación , Transcripción GenéticaRESUMEN
Messenger RNAs are monitored for errors that arise during gene expression by a mechanism called RNA surveillance, with the result that most mRNAs that cannot be translated along their full length are rapidly degraded. This ensures that truncated proteins are seldom made, reducing the accumulation of rogue proteins that might be deleterious. The pathway leading to accelerated mRNA decay is referred to as nonsense-mediated mRNA decay (NMD). The proteins that catalyze steps in NMD in yeast serve two roles, one to monitor errors in gene expression and the other to control the abundance of endogenous wild-type mRNAs as part of the normal repertoire of gene expression. The NMD pathway has a direct impact on hundreds of genetic disorders in the human population, where about a quarter of all known mutations are predicted to trigger NMD.
Asunto(s)
Regulación de la Expresión Génica/fisiología , Enfermedades Genéticas Congénitas/genética , Neoplasias/genética , Terminación de la Cadena Péptídica Traduccional/fisiología , Procesamiento Postranscripcional del ARN , ARN Mensajero/metabolismo , Proteínas de Unión al ARN , Proteínas de Saccharomyces cerevisiae , Animales , Secuencia de Bases , Codón , Proteínas Fúngicas/fisiología , Proteínas del Helminto/fisiología , Humanos , Ratones , Datos de Secuencia Molecular , Mutación Missense , Conformación de Ácido Nucleico , Factores de Terminación de Péptidos/fisiología , ARN Helicasas/fisiología , ARN de Hongos/genética , ARN de Hongos/metabolismo , ARN Mensajero/genética , Saccharomyces cerevisiae/genética , TransactivadoresAsunto(s)
Actitud del Personal de Salud , Enfermeros/psicología , Obesidad/enfermería , Estudiantes de Enfermería/psicología , Adulto , Análisis de Varianza , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Enfermeros/estadística & datos numéricos , Obesidad/psicología , Estudiantes de Enfermería/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
The CTF13 gene codes for a subunit of the kinetochore in Saccharomyces cerevisiae. The temperature-sensitive mutation ctf13-30, which confers reduced fidelity of chromosome transmission, is a G --> A transition causing an amino acid substitution of Lys for Glu146. Strains carrying one chromosomal copy of ctf13-30 fail to grow at the restrictive temperature, whereas a haploid strain carrying two copies of ctf13-30 can grow. Four genes, UPF1, UPF2, UPF3, and ICK1, were represented among extragenic suppressors of ctf13-30. The UPF genes encode proteins that promote rapid decay of pre-mRNAs and mRNAs containing a premature stop codon. Suppressor mutations in these genes restore kinetochore function by causing increased accumulation of ctf13-30 mRNA. They also cause increased accumulation of CYH2 pre-mRNA, which is a natural target of UPF-mediated decay. Mutations in ICK1 restore kinetochore function but have no effect on ctf13-30 mRNA or CYH2 pre-mRNA accumulation. Most importantly, loss of UPF1 function causes increased accumulation of wild-type CTF13 mRNA but has no effect on the mRNA half-life. We propose that UPF-mediated decay modulates the mRNA level of one or more factors involved in CTF13 mRNA expression.